This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of our research has been to combine structural approaches with cell biology and genetic studies in order to better understand fundamental processes that contribute to the growth and differentiation of cells. The structural work entails two lines of experimental efforts of increasing complexity. The first involves understanding the conformational changes underlying the activation (GTP-binding) and deactivation (GTP hydrolysis) of GTP-binding proteins (GTPases). We have been using Cdc42 and related small GTPases (e.g. RhoC), which play critical roles in coordinating cell cycle progression and proliferation with cell shape changes and cell migration, as models for these studies. A second major line of study is directed toward determining the mechanistic and structural basis for the actions of multi-protein complexes that direct the activation of Cdc42 and mediates its cellular responses.